Cholinergic mechanisms have been shown to be involved in determing whether certain myocardial cells will contract spontaneously or whether they will contract in response to impulses transmitted from adjacent cells. Therefore, normal myocardial rhythm relies on proper cholinergic function within the various parts of the heart. This project will continue to biochemically evaluate the function of cholinergic muscarinic receptors in the ventricles of rat hearts in terms of their relative agonist-antagonist affinity characteristics as compared to receptors from nervous tissue (brain) and from hearts of rats subjected to experimental procedures that alter autonomic input to the heart. Changes in affinity characteristics as the result of ionic alterations of the assay medium will also be further studied. Since muscarinic receptors are quite prevalent in ventricular tissue where cholinergic innervation is sparse, it is probable that many of these receptors are not directly associated with nerve terminals and may show altered affinity characteristics different from those receptors associated with nerves. Previous studies with cultured heart cells have shown that activation of muscarinic receptors will increase the spontaneous contraction of certain ventricular cells. Since certain antiarrhythmic drugs interact with muscarine receptors, their effectivensss against ventricular ectopic arrhythmias might be partly explained by this muscarcinic interaction. This hypothesis will be studied further by using isolated perfused rat hearts. Changes will be recorded in contractility and electrical activity in response to various combinations of muscarcinic agonists and antagonists.